A Study to Evaluate the Pharmacokinetics of Divarasib in Healthy Participants and Participants With Impaired Hepatic Function

A Phase 1, Open-Label, Single-Dose, Parallel-Cohort Study to Evaluate the Pharmacokinetics of Divarasib in Subjects With Impaired Hepatic Function

This is a phase 1, open-label, single-dose, parallel-cohort study to determine the pharmacokinetics (PK) of divarasib in healthy participants and participants with varying degrees of hepatic impairment, as defined by Child-Pugh classification.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Divarasib

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, Inc.
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria

• Males or females of non-childbearing potential
• Within body mass index (BMI) range of 18.0 to 45.0 kg/m2

Participants with Hepatic Impairment

• Considered to have mild, moderate, or severe hepatic impairment by Child-Pugh Score classification and has been clinically stable for at least 1 month prior to Screening
• Chronic (>6 months), stable hepatic insufficiency with features of cirrhosis due to any etiology. Participants must also remain stable throughout the Screening period

Key Exclusion Criteria

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator

Participants with Hepatic Impairment

• Have a QTcF >480 msec for males and >490 msec for females at Screening or Check-in. If any parameter is out of range, the ECG may be repeated for confirmation
• Any evidence of progressive liver disease that has worsened or is worsening, as determined by the investigator, within 1 month prior to Screening
• Demonstrated evidence of hepatorenal syndrome
• Ascites requiring paracentesis or other intervention up to 3 days prior to the study
• Hepatic encephalopathy Grade 2 or above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants will receive a single oral dose of Divarasib on Day 1.	Drug: Divarasib; Divarasib will be administered as a single oral dose as specified for the respective cohort.
Experimental: Cohort 2; Participants will receive a single oral dose of Divarasib on Day 1.	Drug: Divarasib; Divarasib will be administered as a single oral dose as specified for the respective cohort.
Experimental: Cohort 3; Participants will receive a single oral dose of Divarasib on Day 1.	Drug: Divarasib; Divarasib will be administered as a single oral dose as specified for the respective cohort.
Experimental: Cohort 4; Participants will receive a single oral dose of Divarasib on Day 1.	Drug: Divarasib; Divarasib will be administered as a single oral dose as specified for the respective cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentration of Divarasib	Day 1 to Day 7
Maximum Observed Concentration (Cmax) of Divarasib	Day 1 to Day 7
Area Under the Concentration-time Curve from Hour 0 to the last measurable concentration (AUC0-t) of Divarasib	Day 1 to Day 7
Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Divarasib	Day 1 to Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events (AEs)	Up to Week 10

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2025
• Primary Completion (Actual): November 27, 2025
• Study Completion (Actual): November 27, 2025

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: GP45713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No